Epilepsy is one of several neurological disorders that can be severely debilitating and/or dangerous. Epilepsy is characterized by the occurrence of seizures, in particular episodic impairment, loss of consciousness, abnormal motor phenomena, psychic or sensory disturbances. It is believed that as many as two to four million Americans may suffer from various forms of epilepsy. Research has found that its prevalence may be even greater worldwide, particularly in less economically developed nations, suggesting that the worldwide figure for epilepsy sufferers may be in excess of one hundred million.
Traditional treatment modalities for epilepsy are moderately efficacious; however, they suffer from several severe drawbacks. One such technique for controlling epilepsy involves the use of dopaminergic agonists or anticholinergic agents. Managing epilepsy using this technique requires iterations in dosing adjustments to balance efficacy and side effects. A number of drugs are approved and available for treating epilepsy, such as lorazopan, diazapan, sodium valproate, phenobarbital/primidone, ethosuximide, gabapentin, phenytoin, and carbamazepine, among others. Unfortunately, these drugs typically have serious side effects, especially toxicity. Further, it is extremely important in most cases to maintain a precise therapeutic serum level to avoid breakthrough seizures (if the dosage is too low) or toxic effects (if the dosage is too high). The need for patient discipline is high, especially when a patient's drug regimen causes unpleasant side effects that the patient may wish to avoid. Moreover, while many epilepsy patients respond well to drug therapy alone, a significant number (at least 20%-30%) do not. For those patients, surgery is presently the best-established and most viable alternative course of treatment.
Commonly practiced surgical approaches for medically refractory epilepsy include surgical resection, such as hemispherectomy, corticectomy, lobectomy and partial lobectomy, and less-radical lesionectomy, transection, and stereotactic ablation. Surgery is not always completely successful and generally has a risk of complications. Further, surgery can result in damage to eloquent (i.e., functionally important) brain regions and the consequent long-term impairment of various cognitive and other neurological functions. Surgical treatments are contraindicated in a substantial number of patients for various reasons. Moreover, of those epilepsy patients who do undergo surgery, many are still not seizure-free after surgery.
Another traditional approach for controlling epilepsy is tissue ablation. Tissue ablation is typically performed via stereotactic neurosurgical procedures, including pallidotomy, thalamotomy, subthalamotomy, and other lesioning procedures. These procedures are only moderately efficatious.
Tissue ablation procedures not only pose inherent surgical risks, but they also suffer from a number of fundamental limitations. One obvious limitation is irreversibility of tissue removal or destruction. Thus, any excessive or inadvertent removal of tissue is final.
Electrical stimulation is an emerging method for treating epilepsy. However, currently approved and available electrical stimulation devices apply continuous electrical stimulation to neural tissue surrounding or near implanted electrodes, and do not perform any detection—simply they do not respond to relevant neurological conditions. One example of an electrical stimulation device is the NeuroCybernetic Prosthesis (NCP) from Cyberonics, Inc. The vagus nerve stimulator (VNS) of this device, for example, applies continuous electrical stimulation to the patient's vagus nerve. The VNS has been found to reduce seizures by about 50% in about 50% of patients tested. Still, a much greater reduction in the incidence of seizures is necessary to provide substantial clinical benefit. Even though the VNS may change the electrical pattern of a seizure, and increasing the interictal time may allow eventual seizure control, some studies in the literature suggest that quality of life is dependent upon the frequency of seizures and not necessarily the interictal time. Hence, the ultimate goal of any antiepileptic therapy should not simply be the facilitation of seizure reduction via changing the seizure pattern or increasing interictal time, but should be actually stopping the seizures.
Electrical stimulation has also been utilized for the treatment of other neurological disorders. For example, a commercially available product, the Activa deep brain stimulator, from Medtronic, Inc., is a pectorally implanted continuous deep brain stimulator intended primarily to treat Parkinson's disease. This device supplies continuous electrical pulses to a selected deep brain structure where an electrode has been implanted in a predetermined neurological region. Chronic high frequency intracranial electrical stimulation is typically used for inhibiting cellular activity in an attempt to functionally mimic the effect of tissue lesioning. Acute electrical stimulation to neural tissue, and electrical recording and impedance measurement from neural tissue are methods commonly used in the identification of brain structures, such as target localization, during neurosurgical operations for the treatment of various neurological disorders.
Continuous stimulation of deep brain structures for the treatment of epilepsy has not met with consistent success. To be effective in terminating seizures, it is believed that stimulation should be performed near the focus of the epileptogenic region. The focus is often in the neocortex, where continuous stimulation may cause significant neurological deficit with clinical symptoms, including loss of speech, sensory disorders, or involuntary motion. Alternatively, the focus of general seizures may move and would thus require insertion of electrodes where the focus moves. This, as well as other conventional treatment modalities, offer some benefit to patients with epilepsy; however, their efficacy is often limited.
Accordingly, research has also been directed toward automatic responsive epilepsy treatment based on a detection of imminent seizure. Neuropace, Inc. is presently developing and conducting clinical trials on an implantable responsive neurostimulator for epilepsy. Once again, there are the risks involved with an implantable system. For episodes where the focus of the seizure moves, or where there is no clear focus, it would be nearly impossible to place electrodes in every location where a seizure focus may be. Compromises must be made to minimize the number of implanted electrodes and maximize the efficacy. Another major concern is that such a device cannot be implanted quick enough during an emergency seizure that is pharmaco-resistant.
Trigeminal nerve stimulation is also a possible method for desynchronizing seizure activity. Advanced Bionics, Inc. is currently developing an implantable device for the treatment of epilepsy that involves the application of electrical stimulation to the trigemnial nerve. As with the vagus nerve, the trigeminal nerve does not project to all areas of the brain and cannot stop all seizures. Once again, this method will have the same concerns for implantable devices as with the above-mentioned devices.
There has been only one anecdotal report in the literature about electroconvulsive therapy (ECT) use in medically intractable seizures in human patients (Griesemer et al., Neurology; 1997 49(5):1389-92): one patient experienced “change in a seizure pattern with cessation at higher intensity,” while the other experienced “decrease in spontaneous seizure frequency”. Surprisingly, no further studies to investigate this methodology in an animal model or in a human clinical series are found. Electroconvulsive therapy (ECT) is performed using conventional EEG electrodes that are not capable of focusing stimulation to a specific volume of biological tissue. To perform ECT, strong muscle relaxants, as well as sedation, are often used. Thus, the patient must be monitored closely.
It has been proposed that if one can apply electrical stimulation at or near the foci, the origin of epileptiform activity, the efficacy of seizure control will be increased. Finding the seizure foci usually involves very expensive and immobile imaging equipment, such as a functional magnetic resonance (fMRI) system. Even with such an elaborate system, real-time analysis of the seizure activity still cannot be achieved. Another means for seizure foci localization is to drill holes into the cranium, and insert electrodes to record and analyze the electrical activity from the brain to determine the location of the foci. The latter technique is extremely invasive, requires a neurosurgeon, and can lead to complications. Similar techniques are applicable for the treatment of Parkinson's disease and other neurological disorders. Another problem that neither of these techniques can overcome is that the foci may move to various other locations. The fMRI and other similar imaging systems, such as positron emission tomography (PET), depend on blood flow changes, which can take many seconds to minutes to occur and thus unable to capture images of fast changing brain activity. A moving seizure focus is at best difficult to map with electrodes inserted into the brain; it may take many electrodes and many holes in the cranium to track the moving foci.
The use of electroencephalogram (EEG) is another approach to epilepsy therapy. EEG is a method for recording brain electrical activity non-invasively from the scalp surface. It can have very good temporal resolution, less than 1.0 ms per sample. EEG can also be a portable system and without being exceedingly expensive. However, EEG does have its limitations, such as the difficulty of localizing, with the type of electrodes used, the sources within the brain due to the smoothing affects of the skull and other body tissue.
There are various methods disclosing localizing mechanisms of biological electrical activity. They all involve post processing of data acquired from either disc or bipolar electrodes. Post processing involves either comparing simulated and measured potentials iteratively, or using a bank of software filters. The solution for source localization by these methods is not in real time, and the use of MRI/CT data is often necessary. In one example, magnetoencephalographic (MEG) is used to localize sources in the brain (see e.g., U.S. Pat. No. 6,697,660). It has high temporal resolution similar to EEG, however, it is very costly, not portable, and requires a special room to facilitate its use.
In another example, multiple spatial filters are used for the localization of electrical sources from EEG signals in the brain (see e.g., U.S. Pat. No. 5,263,488). This technique requires post processing and is limited in resolution due to the use of conventional EEG electrodes.
In another example involving the localization of electrical sources in the brain using EEG, (MRI another method of imaging the head is used for determining the shape and thickness of the scalp, skull, cerebrospinal fluid, and brain (see e.g., U.S. Pat. No. 5,331,970). Once this information is acquired, then a computer model is developed and a mathematical deblurring algorithm is applied to estimate the location of the sources on the cortical surface of the brain. This requires much post processing time to determine where the sources originate from and cannot be used in real-time.
A similar approach has been utilized for imaging electrical activity of the heart (see e.g., U.S. Pat. No. 6,856,830). This method involves the recording of ECG on the body surface, obtaining an MRI or CT image of the patient's torso, and entering both components into a heart-torso model. The ext step of this method involves post processing, whereby, the body surface potentials are calculated for sources in the heart and compared to the measured body surface potentials. This procedure must be repeated iteratively until the two components are within a given preset error range. Hence, this process cannot be performed in real-time. Further, there is no definite localization of the sources, and, distortion, due to global sources, is evident because the recording is performed with ordinary ECG electrodes.
In another example, regular EEG recording techniques and/or MEG are used, and restrictions are placed on the location where the brain electrical activity may be occurring (see e.g., U.S. patent application 20030093004). This approach is limited by the fact that the location of the activity must be known prior to the performance of this technique in order for this type of a system to resolve an inverse localization from the surface potentials. Further, this technique suffers from the blurring effects of the heads volume conductor.
In another example, electrical impedance plethysmography (EIP) is suggested for localizing electrical sources inside biological tissue (see e.g., U.S. patent application 20020038095). In EIP, impedance characterizations that are made over a period of time are used to localize changes in the body tissue. Electrical stimulation is injected into tissue and return signals are measured to determine the impedance. As sources below the surface interact with the injected signals, a map of conductivities is developed, and a model is assembled from these conductivities to iteratively localize sources in the tissue. This type of device is still dependent on typical EEG electrodes, which accept global signals distorting the localization process.
As the current approaches to therapy, which include systems that are presently available and those that are under development, such as drugs, surgery and implantable systems, present a variety of complications, there is a need for a system and method to non-invasively detect, treat, and prevent neurological disorders, particularly epilepsy.